The human immunodeficiency virus type 1 (HIV-1) has emerged in the form of many different strains termed subtypes (A-K) throughout the globe. While all subtypes are pathogenic, subtypes C and A have demonstrated peculiar evolutionary patterns, in terms of their global and in vivo distribution. The NIH Vaccine Research Center (VRC) is developing HIV/AIDS vaccine products that will target subtypes A, B and C with the goal of eliciting broadly neutralizing antibody and cross-reacting cellular responses. As these subtypes comprise approximately 85-90% of all HIV infections world-wide, understanding their biology and pathogenic potential may aid in our efforts to develop effective antiviral agents including vaccines. It is currently not known how individuals immunologically respond to HIV-1 non-B subtype infections. This may be critical in our efforts to develop vaccines that will be broadly cross-reactive to all of the various subtypes and clades of HIV-1 worldwide. To address these issues, the HIV section of the Viral Pathogenesis Laboratory (VPL) will examine cellular responses to HIV-1 non-B subtypes in collaboration with Nigerian scientist(s) and within African immigrant populations here in the U.S. In addition, we will pursue studies to examine primary HIV-1 subtype C and A isolates in vitro according to cytopathicity, viral entry characteristics and resistance to antiviral properties of various entry and fusion based inhibitors